N-(cyanomethyl)isonicotinamide | 1184796-18-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(cyanomethyl)isonicotinamide
• 英文别名: N-(cyanomethyl)pyridine-4-carboxamide
• CAS: 1184796-18-6
• 化学式: C₈H₇N₃O
• 分子量: 161.163
• InChiKey: NQSJOBCWGOKIMH-UHFFFAOYSA-N

物化性质

• 沸点：
  454.0±25.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(cyanomethyl)isonicotinamide 在 diphosphorus pentasulfide 、 三乙酰氧基硼氢化钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 45.75h， 生成 (S)-3-phenyl-N-(2-(pyridin-4-yl)thiazol-5-yl)-2-((thiazol-5-ylmethyl)amino)propanamide
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854
• 作为产物：
  描述：

  异烟酸 、 氨基乙腈盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以99%的产率得到N-(cyanomethyl)isonicotinamide
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854

文献信息

• PHENYLANALINE AMIDE DERIVATIVES USEFUL FOR TREATING INSULIN-RELATED DISEASES AND CONDITIONS
  申请人：Du Xiaohui

  公开号：US20120115811A1

  公开（公告）日：2012-05-10

  Provided herein are compounds of formula I: wherein A, B, X, R 1 , R 2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

  本文所提供的是I式化合物：其中A、B、X、R1、R2和下标n如下所述。本文还提供了包含该化合物的组合物，以及使用它们的方法，例如用于治疗2型糖尿病和2型糖尿病相关疾病的方法。
• Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions
  申请人：Du Xiaohui

  公开号：US08785468B2

  公开（公告）日：2014-07-22

  Provided herein are compounds of formula I: wherein A, B, X, R1, R2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

  本文提供的是I式化合物，其中A、B、X、R1、R2和下标n的定义如下所述。还提供了包含这些化合物的组合物，以及它们的使用方法，例如用于治疗2型糖尿病和2型糖尿病相关疾病。
• N-cyanoalkylisonicotinamide derivatives
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP0246507A1

  公开（公告）日：1987-11-25

  Disclosed herein is a compound of the formula: wherein X is halogen, lower alkoxy or lower alkylthio, Y is hydrogen or chloro, R₁ is hydrogen, lower alkyl, cyanomethyl, phenyl or benzyl, R₂ is hydrogen, C₁ ∿ C₇ - alkyl, C₃ ∿ C₆ - cycloalkyl, lower alkoxy, phenyl, phenoxyphenyl, furyl, thienyl or benzyl and n = 1 or 2 with a proviso that X and Y are not chloro at the same time, a fungicidal or bactericidal composition containing said compound as an effective component, a method for preventing diseases of agricultural or horticultural plant and a method for manufacturing said compound.

  本文公开了一种式化合物： 其中 X 是卤素、低级烷氧基或低级烷硫基、 Y 是氢或氯 R₁ 是氢、低级烷基、氰基甲基、苯基或苄基、 R₂ 是氢、C₁ ∿ C₇ - 烷基、C₃ ∿ C₆ - 环烷基、低级烷氧基、苯基、苯氧基苯基、呋喃基、噻吩基或苄基，且 n = 1 或 2 一种含有上述化合物作为有效成分的杀真菌或杀细菌组合物、一种预防农业或园艺植物病害的方法以及一种制造上述化合物的方法。
• [EN] PHENYLALANINE AMIDE DERIVATIVES USEFUL FOR TREATING INSULIN-RELATED DISEASES AND CONDITIONS<br/>[FR] DÉRIVÉS DE LA PHÉNYLALANINE-AMIDE UTILES POUR LE TRAITEMENT DE MALADIES ET ÉTATS LIÉS À L'INSULINE
  申请人：AMGEN INC

  公开号：WO2010093849A3

  公开（公告）日：2010-10-28
• US4804762A
  申请人：——

  公开号：US4804762A

  公开（公告）日：1989-02-14